In the human brain, several ten billion nerve cells constitute a complex network; however, if the mechanism for neurogenesis from a few nerve stem cells is not taken into account, the cell count basically continues to decrease after birth. During the long lifespan reportedly extending to hundred and several tens of years, the brain works to maintain survival by making the best use of a variety of protective mechanisms against a variety of extraneous and endogenous stresses. In the protective mechanisms possessed by the brain itself, nerve-glia and nerve-nerve communities are working while influencing each other to maintain their sophisticated roles. The best known nerve protecting mechanism is functionalized by molecules such as neurotrophic factors and cytokines. These neurotrophic factors are known to have the function of suppressing programmed nerve cell death (apoptosis), which is seen under a variety of stress conditions. Another mechanism is neurogenesis; although it has recently been reported that neurogenesis is accentuated under cerebral ischemic stress, which, however, is expected to be insufficient to compensate for large amounts of nerves undergoing cell death.
During cerebral ischemia, necrosis, which is destructive cell death, is observed in the core portion at the center of ischemia; because this cell death involves the discharge of cell content to the outside, the cytotoxic action should essentially further diffuse to the surroundings. Several days later, however, apoptosis-specific phenomena, such as cell fragmentation, condensation, and phagocytosis by microglia and the like, are observed in the surrounding region known as the penumbra. This apoptosis seen in the penumbra is thought to function as a kind of protective mechanism that prevents the entire brain from being injured, by localizing the injured site (see Non-patent Document 1). The present inventor found for the first time that the above-described conversion of the form of cell death from necrosis to apoptosis observed during cerebral ischemia is caused by prothymosin α (see Non-patent Document 2).
By the way, cerebral stroke is an important disease ranking the third in mortality rate and the first as an etiology of bed-ridden state among Japanese, being a disease developing as a result of cerebral ischemia. In cerebral stroke, treatment in the acute stage is said to be important in the meaning of improving the prognosis. A major therapeutic method that is currently drawing attention involves thrombolytic agents, including plasminogen activators (hereinafter denoted as “tPA”); the use thereof is limited to within 3 hours, patients that can enjoy the benefit accounting for only about ten-odd percent (see Non-patent Document 3). This is because the blood-brain barrier embrittles with elapse of time after cerebral stroke, and hence because the risk of hemorrhagic cerebral stroke increases with use of thrombolytic agents such as tPA. However, no substance possessing the action of protecting the blood-brain barrier against the embrittlement of the blood-brain barrier that can be used along with thrombolytic agents has been found yet.
The present inventor recently found for the first time that prothymosin α is a substance possessing protecting action against nerve cell death, and capable of mitigating cerebral stroke disorders by this nerve cell death suppressing effect (see Patent Document 1). The present inventor and others also found that prothymosin α has the effect of suppressing cerebral stroke and ischemic glaucoma in mice and rats (see Non-patent Documents 4-6).